Two-photon endoscopic scanning assembly for inflammatory disease detection

Abstract

An endoscopic imaging device is described that achieves longitudinal axis (z-axis) scanning into a tissue or sample, using a piezoelectric microactuator. In some configurations, additional lateral (xy-plane) scanning is also achieved, to allow for the creation of full three-dimensional imaging, ex vivo or in vivo. The techniques may be used to image and diagnosis allergic rhinitis and eosinophilic esophagitis in tissue.

What is claimed: 
     
       1. An endoscopic device for illuminating a sample over a 3-dimensional volume, the device comprising:
 a connector stage for receiving an input beam of short pulses; 
 an xy-scanning stage coupled to receive the input beam of short pulses and scan the short pulses for movement in a lateral direction across an xy-plane of the sample; 
 an actuator stage coupled to scan the short pulses for movement in a z-axis direction of the sample, where the actuator stage comprises a piezoelectric stage capable of producing a first displacement, an amplification stage mechanically coupled to the piezoelectric stage for amplifying the first displacement into a second displacement, and a lens mounting stage coupled to the amplification stage, where the piezoelectric stage, the amplification stage, and the lens mounting stage form an integrated MEMS assembly; and 
 a lens mounted on the lens mounting stage for scanning the input beam across the 3-dimensional volume within the sample. 
 
     
     
       2. The endoscopic device of  claim 1 , wherein the amplification stage comprises a lever amplifier for translating piezoelectric movement into at least partially transverse movement and mechanically coupled to a chevron stage for translating and amplifying the translated movement into longitudinal movement. 
     
     
       3. The endoscopic device of  claim 2 , wherein the chevron stage comprises two chevron beams coupled to tips of lever beams of the lever amplifier. 
     
     
       4. The endoscopic device of  claim 2 , wherein the piezoelectric stage is formed of a lead-zirconate-titanate (PZT) assembly rigidly coupled to one end of a base and movably coupled to the amplification stage, wherein the amplification stage is positioned for movement along the base. 
     
     
       5. The endoscopic device of  claim 2 , wherein the lens mounting stage comprises a lens platform and a spring system coupling the lens platform to the chevron stage. 
     
     
       6. The endoscopic device of  claim 1 , further comprising a gradient index (GRIN) lens at sampling end of the endoscopic device for coupling the light into the sample. 
     
     
       7. The endoscopic device of  claim 1 , further comprising an external controller coupled to the xy-scanning stage and to the actuator stage to control scanning of the short pulses within the 3-dimensional volume of the sample. 
     
     
       8. The endoscopic device of  claim 1 , wherein the sample is a biological sample. 
     
     
       9. The endoscopic device of  claim 8 , wherein the biological sample is tissue. 
     
     
       10. The endoscopic device of  claim 1 , wherein the sample is a non-biological material. 
     
     
       11. The endoscopic device of  claim 10 , wherein the non-biological material comprises a plastic, metal, or semiconductor material. 
     
     
       12. The endoscopic device of  claim 1 , wherein the actuator stage comprises two opposing actuators housed, along with the xy scanning stage and the lens, within a housing. 
     
     
       13. The endoscopic device of  claim 12 , wherein the actuator stage scans the short pulses over a range of 0 to 500 μm in the z-axis. 
     
     
       14. The endoscopic device of  claim 13 , wherein the actuator stage has a scanning frequency of 0 to 500 Hz. 
     
     
       15. The endoscopic device of  claim 13 , wherein the actuator stage has a scanning frequency of greater than 500 Hz.